Antibiotics and Clostridium difficile: cause and cure.
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Biomedical subjects
Publications and source records attributed to Christina M Surawicz.
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Probiotics have been studied in a variety of GI infections, and are an appealing concept given their favorable safety profiles. Several placebo-controlled trials indicated that lactobacilli have a suppressive effect on H pylori infection. Although some studies reported improvement in H pylori eradication, others failed to confirm this. Controlled trials support the use of Lactobacillus GG and S boulardii for the prevention of AAD, and have demonstrated the effectiveness of S boulardii as adjunctive therapy for RCDAD. Several placebo-controlled trials showed a reduction in the severity and duration of acute diarrhea in children with use of Lactobacillus GG. Studies of probiotics for the prevention of traveler's diarrhea yielded conflicting results, and their routine use cannot be recommended in this setting. Preliminary evidence suggests a potential role for reducing secondary pancreatic infections, although conclusive evidence is not available at this time. Additional clinical trials are indicated to define the role of probiotics further before wide-spread use can be recommended.
BACKGROUND: A 69-year-old white woman presented to our gastroenterology department with loose stools, daily fecal incontinence and weight loss. She had a 3-year history of fecal incontinence, which had increased in frequency and severity in the year before her most recent presentation. Prior diagnostic workup included anorectal manometry, revealing global sphincter dysfunction, which improved slightly with biofeedback therapy, and colonoscopy, which proved unremarkable. At the time of referral, the patient was taking loperamide 2mg once daily. INVESTIGATIONS: Physical examination, fecal fat stain, abdominal CT scan, therapeutic trial of pancreatic enzymes, celiac disease serologic tests, and upper endoscopy with small-bowel biopsy. DIAGNOSIS: Celiac disease. MANAGEMENT: Gluten-free diet.
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Diarrhea is a well-known complication of antibiotic therapy. Rates of antibiotic-associated diarrhea (AAD) vary from 5 to 25%. Some antibiotics are more likely to cause diarrhea than others, specifically, those that are broad spectrum and those that target anaerobic flora. This paper reviews the effects of antibiotics on the fecal flora as well as host factors which contribute to AAD. Clinical features and treatment of AAD are also described. Prevention of AAD rests on wise antibiotic policies, the use of probiotics and prevention of acquisition in the hospital setting. Data from clinical trials suggest that poorly absorbed antimicrobials might have a decreased risk of causing AAD and Clostridium difficile-associated disease, as concluded from studies of antibiotics used for preoperative bowel decontamination and poorly absorbed antibiotics used for traveler's diarrhea. Controlled trials would prove this but are not yet available. Probiotics may be a good adjunct to poorly absorbed antibiotics to minimize the risk of diarrhea associated with antibiotics.
Recurrent Clostridium difficile-associated disease (RCDAD) is a difficult treatment problem--once a patient has one recurrence of the disease the likelihood of further recurrences is markedly increased. Repeat antibiotics are usually indicated, either metronidazole or vancomycin. Tapering and pulsing the antibiotic dose after a 10-day standard course decreases the incidence of recurrences compared with abruptly stopping antibiotics after a simple 10-day course. If recurrences continue after two courses of metronidazole, vancomycin may be preferable to avoid the risk of neurotoxicity that is associated with prolonged metronidazole use. There is also a role for probiotics in the treatment of RCDAD; Saccharomyces boulardii has been shown to decrease recurrences by about 50%, especially when combined with high-dose vancomycin. Other microbiologic approaches include the restoration of normal colonic flora by fecal enema or by nasogastric tube, but these have not been studied in controlled trials. In addition, there are numerous new treatment approaches that are under development, including a vaccine, which promise to aid the future treatment of RCDAD as well as prevention of initial CDAD.
OBJECTIVES: To assess safety and acceptability of Reality condoms for anal sex among men who have sex with men. METHODS: Crossover study among HIV-seroconcordant (33 HIV-negative and 5 HIV-positive) monogamous male couples, randomized to latex male and Reality condom use with anal sex. RESULTS: Slippage with removal was reported more frequently with Reality than male latex condoms [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.2-5.8 for receptive partners and OR, 34.1; 95% CI, 13.8-84.1 for insertive partners]. Receptive partners more frequently reported pain or discomfort (OR, 5.0; 95% CI, 2.6-9.4) and rectal bleeding (OR, 1.9; 95% CI, 0.9-4.1) with Reality condoms than male condoms. Over 20% reported willingness to use the Reality condom in the future with a partner of unknown HIV status; willingness was associated with past problems with male condoms and no problems with Reality condoms among receptive partners, and with past use of Reality condoms and HIV seropositivity among insertive partners. CONCLUSIONS: Men reported more frequent problems with Reality condoms than male latex condoms used for anal intercourse, particularly slippage, discomfort, and rectal bleeding. Design modifications, training, and research on the clinical significance of safety outcomes are needed for use of Reality condoms with anal sex.
Probiotics are living organisms which, when ingested, have a beneficial therapeutic effect. Examples are bacteria, especially Lactobacillus rhamnosus GG, and the yeast Saccharomyces boulardii. Controlled trials indicate a benefit of both of these in the prevention of antibiotic-associated diarrhoea. Other less effective probiotics are Lactinex, Enterococcus faecium and bifidobacteria. In the difficult clinical problem of recurrent Clostridium difficile disease, S. boulardii as an adjunct to antibiotics has shown benefit in controlled trials. There is, however, less convincing evidence for the efficacy of Lactobacillus GG in this disease. Additional controlled trials and safety studies are needed before there can be a widespread endorsement of probiotics for these two conditions.
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OBJECTIVE: The aim of the present study was to assess the correlation of Triage Micro Clostridium difficile Panel and toxin B cytotoxicity assay with the clinical diagnosis of C. difficile diarrhea. METHODS: The subjects evaluated were 98 patients with diarrhea for whom stool was submitted for testing for C. difficile. Clinical symptoms prompting evaluation, laboratory values, comorbid illness, and treatment outcomes that provided clinical insight into the etiology of the diarrhea were recorded. These data were then reviewed by two experienced clinical gastroenterologists who were blinded to the results of the Triage enzyme immunoassay and cytotoxin B assay. The final diagnosis of C. difficile diarrhea was based on the patient's clinical evaluation and symptoms, treatment, and subsequent outcome. RESULTS: Of 98 patients evaluated, 33 were diagnosed with C. difficile diarrhea by clinical criteria. The toxin B assay displayed 88% sensitivity and 100% specificity and positive predictive value. The toxin A component of the Triage Panel displayed 45% sensitivity but 98% specificity and 94% positive predictive value. The common antigen had 97% sensitivity and 95% negative predictive value. Among the 45 patients with only a common antigen detected, the most common diagnoses for diarrhea were chemotherapy-related, antibiotic-related diarrhea, and graft versus host disease. CONCLUSIONS: Our data show that both the Triage Micro C. difficile Panel and cytotoxin B for C. difficile have a high positive predictive value and negative predictive value for C. difficile diarrhea. The Triage Micro C. difficile Panel provides a reasonable alternative to the cytotoxin B assay in the assessment of clinically relevant C. difficile. The Triage Micro C. difficile Panel is less labor intensive and less expensive than cytotoxin B assay. The panel approach improves on the individual assay performances by increasing sensitivity and negative predictive value. When both common antigen and toxin A are positive, the likelihood of C. difficile diarrhea is high; conversely, when both results are negative, the likelihood of C. difficile diarrhea is low.
OBJECTIVE: There is currently uncertainty as to the best treatment for patients with recurrent episodes of Clostridium difficile disease (RCDD). Our objective was to evaluate the success of treatment strategies in a cohort of 163 RCDD patients. METHODS: Data were used from patients who had participated in the placebo arm in two national referral clinical trials evaluating a new combination treatment. Patients with active RCCD were enrolled, prescribed either vancomycin or metronidazole, and randomized to either the investigational biological or a placebo. All patients were observed for at least 2 months for a subsequent episode of RCCD. RESULTS: Of the 163 cases, 44.8% recurred. A tapering course of vancomycin resulted in significantly fewer recurrences (31%, p = 0.01), as did pulsed dosing of vancomycin (14.3%, p = 0.02). A trend (p = 0.09) for a lower recurrence frequency was observed for high-dose (> or =2 g/day) vancomycin and low-dose (< or =1 g/day) metronidazole. Vancomycin was significantly more effective in clearing C. difficile culture and/or toxin by the end of therapy than metronidazole (89% vs 59%, respectively; p < 0.001). CONCLUSIONS: These data show that tapered or pulsed dosing regimens of vancomycin may result in a significantly better cure of RCDD. The persistence of C. difficile spores suggests that additional strategies to restore the normal colonic microflora may also be beneficial.
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Probiotics are living organisms that have a beneficial therapeutic effect on the host when ingested. The bacteria Lactobacillus GG and the yeast Saccharomyces boulardii have been shown in controlled trials to prevent antibiotic-associated diarrhea. Prebiotics are non-living, indigestible polysaccharides metabolized in the intestine that induce physical and bacteriologic musocal modifications. Rather than introducing exogenous bacteria into the intestinal millieu, prebiotics stimulate certain indigenous bacteria already resident in the gut.